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A lead candidate functional single nucleotide polymorphism within the WARS2 gene associated with waist-hip-ratio does not alter RNA stability.

ABSTRACT: We have prioritised a single nucleotide polymorphism (SNP) rs2645294 as one candidate functional SNP in the TBX15-WARS2 waist-hip-ratio locus using posterior probability analysis. This SNP is located in the 3' untranslated region of the WARS2 (tryptophanyl tRNA synthetase 2, mitochondrial) gene with which it has an expression quantitative trait in subcutaneous white adipose tissue. We show that transcripts of the WARS2 gene in a human white adipose cell line, heterozygous for the rs2645294 SNP, showed allelic imbalance. We tested whether the rs2645294 SNP altered WARS2 RNA stability using three different methods: actinomycin-D inhibition and RNA decay, mature and nascent RNA analysis and luciferase reporter assays. We found no evidence of a difference in RNA stability between the rs2645294 alleles indicating that the allelic expression imbalance was likely due to transcriptional regulation.

SUBMITTER: Muso M

PROVIDER: S-EPMC7695619 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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A lead candidate functional single nucleotide polymorphism within the WARS2 gene associated with waist-hip-ratio does not alter RNA stability.

Mušo Milan M Dumbell Rebecca R Pulit Sara S Sinnott-Armstrong Nasa N Laber Samantha S Zolkiewski Louisa L Bentley Liz L Claussnitzer Melina M Cox Roger D RD

Biochimica et biophysica acta. Gene regulatory mechanisms 20200930 11

We have prioritised a single nucleotide polymorphism (SNP) rs2645294 as one candidate functional SNP in the TBX15-WARS2 waist-hip-ratio locus using posterior probability analysis. This SNP is located in the 3' untranslated region of the WARS2 (tryptophanyl tRNA synthetase 2, mitochondrial) gene with which it has an expression quantitative trait in subcutaneous white adipose tissue. We show that transcripts of the WARS2 gene in a human white adipose cell line, heterozygous for the rs2645294 SNP, ...[more]

PMID: 33007465

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Project description:BackgroundWaist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) are all independent predictors of cardio-metabolic risk and therefore important in HIV/AIDS patients on antiretroviral therapy at risk of increased visceral adiposity. This study aimed to assess the extent of agreement between these parameters and the body mass index (BMI), as anthropometric parameters and in classifying cardio-metabolic risk in HIV/AIDS patients.MethodsA secondary analysis of data from a cross-sectional study involving 200 HIV/AIDS patients was done. Anthropometric parameters were measured from participants using standard guidelines and central obesity defined according to recommended criteria. Increased cardio-metabolic risk was defined according to the standard cut-off values for all four parameters. Data were analyzed using STATA version 14.1.ResultsThe prevalence of WC-defined central obesity, WHR-defined central obesity and WHtR > 0.50 were 33.5%, 44.5% and 36.5%, respectively. The prevalence of BMI-defined overweight and obesity was 40.5%. After adjusting for gender and HAART status, there was a significant linear association and correlation between WC and BMI (regression equation: WC (cm) = 37.184 + 1.756 BMI (Kg/m2) + 0.825 Male + 1.002 HAART, (p < 0.001, r = 0.65)), and between WHtR and BMI (regression equation: WHtR = 0.223 + 0.011 BMI (Kg/m2)- 0.0153 Male + 0.003 HAART, (p < 0.001, r = 0.65)), but not between WHR and BMI (p = 0.097, r = 0.13). There was no agreement between the WC, WHtR and BMI, and minimal agreement between the WHR and BMI, in identifying patients with an increased cardio-metabolic risk.ConclusionDespite the observed linear association and correlation between these anthropometric parameters, the routine use of WC, WHR and WHtR as better predictors of cardio-metabolic risk should be encouraged in these patients, due to their minimal agreement with BMI in identifying HIV/AIDS patients with increased cardio-metabolic risk. HAART status does not appear to significantly affect the association between these anthropometric parameters.

Project description:BackgroundLittle is known about the long-term shifts in distributions of three abdominal-obesity-related indicators, waist circumference (WC), waist-to-hip ratio (WHpR) and waist-to-height ratio (WHtR) among Chinese adults. Traditional mean regression models used in the previous analyses were limited in their ability to capture cross-distribution among effects. The current study aims to describe the shift in distribution of WC, WHpR, and WHtR over a period of 18 years (1993-2011) in China, and to reveal quantile-specific associations of the three indicators with key covariates.MethodsLongitudinal data from seven waves of the China Health and Nutrition Surveys (CHNS) in 1993, 1997, 2000, 2004, 2006, 2009 and 2011 were analyzed. The LMS method was used to illustrate the gender-specific quantile curves of WC, WHtR and WHpR over age. Separate gender-stratified longitudinal quantile regressions were employed to investigate the effect of important factors on the trends of the three indicators.ResultsA total of 11,923 participants aged 18-65 years with 49,507 observations were included in the analysis. The density curves of WC, WHtR and WHpR shifted to right and became wider. The three outcomes all increased with age and increased more at upper percentiles. From the multivariate quantile regression, physical activity was negatively associated in both genders; smoking only had a negative effect on male indicators. Education and drinking behavior both had opposite effects on the three indicators between men and women. Marital status and income were positively associated with the shifts in WC, WHtR and WHpR in male and female WC, while urbanicity index had a positive effect on three outcomes in men but inconsistent effect among female outcomes.ConclusionsThe abdominal-obesity related indicators of the Chinese adults experienced rapid growth according to our population-based, age- and gender-specific analyses. Over the 18-year study period, major increases in WC, WHtR and WHpR were observed among Chinese adults. Specifically, these increases were greater at upper percentiles and in men. Age, physical activity, energy intake, drinking, smoking, education, income and urbanicity index were associated with elevated abdominal obesity indicators, and the effects differed among percentiles and between genders.

Dataset Information

A lead candidate functional single nucleotide polymorphism within the WARS2 gene associated with waist-hip-ratio does not alter RNA stability.

Publications

A lead candidate functional single nucleotide polymorphism within the WARS2 gene associated with waist-hip-ratio does not alter RNA stability.

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